...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The γ-secretase-generated intracellular domain of β-amyloid precursor protein binds Numb and inhibits Notch signaling
【24h】

The γ-secretase-generated intracellular domain of β-amyloid precursor protein binds Numb and inhibits Notch signaling

机译：γ-分泌酶生成的β-淀粉样蛋白前体蛋白的胞内结构域结合Numb并抑制Notch信号传导

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The β-amyloid precursor protein (APP) and the Notch receptor undergo intramembranous proteolysis by the Presenilin-depen-dent γ-secretase. The cleavage of APP by γ-secretase releases amyloid-β peptides, which have been implicated in the pathogen-esis of Alzheimer's disease, and the APP intracellular domain (AID), for which the function is not yet well understood. A similar γ-secretase-mediated cleavage of the Notch receptor liberates the Notch intracellular domain (NICD). NICD translocates to the nucleus and activates the transcription of genes that regulate the generation, differentiation, and survival of neuronal cells. Hence, some of the effects of APP signaling and Alzheimer's disease pathology may be mediated by the interaction of APP and Notch. Here, we show that membrane-tethered APP binds to the cytosolic Notch inhibitors Numb and Numb-like in mouse brain lysates. AID also binds Numb and Numb-like, and represses Notch activity when released by APP. Thus, γ-secretase may have opposing effects on Notch signaling; positive by cleaving Notch and generating NICD, and negative by processing APP and generating AID, which inhibits the function of NICD.
机译：β-淀粉样蛋白前体蛋白（APP）和Notch受体通过早老素依赖性的γ-分泌酶进行膜内蛋白水解。 γ-分泌酶对APP的裂解会释放淀粉样β肽，这与阿尔茨海默氏病的病原菌病以及APP胞内域（AID）有关，而后者的功能尚不清楚。 Notch受体的类似γ-分泌酶介导的裂解可释放Notch细胞内结构域（NICD）。 NICD易位至细胞核并激活调节神经元细胞生成，分化和存活的基因的转录。因此，APP信号传导和阿尔茨海默氏病病理学的某些作用可能是由APP和Notch的相互作用介导的。在这里，我们显示膜拴的APP绑定到小鼠脑裂解物中的胞质Notch抑制剂Numb和Numb-like。 AID还可以绑定Numb和类似Numb的物体，并在被APP释放时抑制Notch活性。因此，γ-分泌酶可能对Notch信号传导具有相反的作用。切割Notch产生NICD呈阳性，通过处理APP产生AID呈阴性，这抑制了NICD的功能。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号